Pretreatment Positron Emission Tomography Scans Research Articles

Comparison of lung cancer aggressiveness in patients who never smoked compared to those who smoked

ObjectivesTo determine whether radiographic measures of tumor aggressiveness differ by smoking status. Materials and MethodsAll patients diagnosed with non-small-cell lung cancer(NSCLC) ≤ 30 mm in maximum diameter, without clinical evidence of metastasis who had both pre-treatment PET scans and two CT scans at least 90 days apart in a prospective cohort, the Initiative for Early Lung Cancer Research on Treatment(IELCART) at Mount Sinai between 2016 and 2020 were identified. Comparison of two measures of tumor aggressiveness, positron emission tomography(PET) SUVmax and tumor volume doubling time(VDT) by smoking status was performed. ResultsOf 417 patients identified, 158 patients had pre-treatment PET scans and at least two CT scans available. The two measures of tumor aggressiveness, SUVmax and VDT values were significantly different between patients who had never smoked and those who smoked: patients who never smoked had lower median SUVmax[2.5(IQR: 1.1–4.8) vs. 4.2(IQR:2.1–9.2),p = 0.002] and longer median VDT[(372.6 days vs. 225.6 days,p = 0.001)] compared to those who smoked. Using multivariable analyses, when adjusting for age and sex alone, SUVmax(p = 0.004) and VDT(p = 0.0001) remained significantly different by smoking status. The final multivariable analysis, adjusted for all three co-variates(sex, age and tumor histology) showed no significant difference in SUVmax and VDT by smoking status [SUVmax(p = 0.25) and VDT(p = 0.06)]. ConclusionSmoking history does not influence VDT or PET SUVmax measures of lung cancer aggressiveness.

Deep learning based time-to-event analysis with PET, CT and joint PET/CT for head and neck cancer prognosis

ObjectivesRecent studies have shown that deep learning based on pre-treatment positron emission tomography (PET) or computed tomography (CT) is promising for distant metastasis (DM) and overall survival (OS) prognosis in head and neck cancer (HNC). However, lesion segmentation is typically required, resulting in a predictive power susceptible to variations in primary and lymph node gross tumor volume (GTV) segmentation. This study aimed at achieving prognosis without GTV segmentation, and extending single modality prognosis to joint PET/CT to allow investigating the predictive performance of combined- compared to single-modality inputs. MethodsWe employed a 3D-Resnet combined with a time-to-event outcome model to incorporate censoring information. We focused on the prognosis of DM and OS for HNC patients. For each clinical endpoint, five models with PET and/or CT images as input were compared: PET-GTV, PET-only, CT-GTV, CT-only, and PET/CT-GTV models, where -GTV indicates that the corresponding images were masked using the GTV contour. Publicly available delineated CT and PET scans from 4 different Canadian hospitals (293) and the MAASTRO clinic (74) were used for training by 3-fold cross-validation (CV). For independent testing, we used 110 patients from a collaborating institution. The predictive performance was evaluated via Harrell's Concordance Index (HCI) and Kaplan-Meier curves. ResultsIn a 5-year time-to-event analysis, all models could produce CV HCIs with median values around 0.8 for DM and 0.7 for OS. The best performance was obtained with the PET-only model, achieving a median testing HCI of 0.82 for DM and 0.69 for OS. Compared with the PET/CT-GTV model, the PET-only still had advantages of up to 0.07 in terms of testing HCI. The Kaplan-Meier curves and corresponding log-rank test results also demonstrated significant stratification capability of our models for the testing cohort. ConclusionDeep learning-based DM and OS time-to-event models showed predictive capability and could provide indications for personalized RT. The best predictive performance achieved by the PET-only model suggested GTV segmentation might be less relevant for PET-based prognosis.

Negative Association of Smoking History With Clinically Manifest Cardiac Sarcoidosis: A Case-Control Study

BackgroundThe etiology of sarcoidosis is still unknown and is likely related to a genetic susceptibility to unidentified environmental trigger(s). Our group and others have extensively described a specific phenotype of primarily Caucasian patients who have clinically manifest cardiac sarcoidosis (CS). In this study, we sought to explore whether smoking is associated with this specific phenotype of sarcoidosis. MethodsWe performed a case-control study. Cases with clinically manifest CS were prospectively enrolled in the Cardiac Sarcoidosis Multi-Center Prospective Cohort Study (CHASM-CS registry; NCT01477359) and answered a standardized smoking history questionnaire. Cases were matched 10:1 with controls from the Ontario Health Study. Pretreatment positron emission tomography scans with 18F-fluorodeoxyglucose were compared for smokers vs nonsmokers. ResultsEighty-seven cases met the inclusion criteria. A total of 82 of 87 (94.3%) answered the questionnaire and were matched with 820 controls. A clear negative association of sarcoidosis and smoking was found, with 23 of 82 CS cases (28.0%) being current or ex-smokers, vs 392 of 820 controls (47.8%; P = 0.0006). CS patients with a smoking history had significantly less lifetime consumption (8.31 ± 9.20 pack-years) than the controls (15.34 ± 10.84 pack-years; P < 0.003). On 18F-fluorodeoxyglucose-positron emission tomography scan, the mean standardized uptake value of the left ventricle was 4.2 ± 8.98 in lifetime nonsmokers vs 2.89 ± 2.07 in patients with a smoking history (P < 0.0001). ConclusionsWe describe a strong negative association between smoking history and clinically manifest CS. Nonsmokers had more severe myocardial inflammation (greater mean standardized uptake value of the left ventricle) than did patients with a smoking history. Further research is needed to understand these associations and whether they have therapeutic potential.

A positron emission tomography radiomic signature for distant metastases risk in oropharyngeal cancer patients treated with definitive chemoradiotherapy.

Disease recurrence and distant metastases (DM) are major concerns for oropharyngeal cancer (OPC) patients receiving definitive chemo-radiotherapy. Here, we investigated whether pre-treatment primary tumor positron emission tomography (PET) features could predict progression-free survival (PFS) or DM. Primary tumors were delineated on pre-treatment PET scans for patients treated between 2005 and 2018 using gradient-based segmentation. Radiomic image features were extracted, along with SUV metrics. Features with zero variance and strong correlation to tumor volume, stage, p16 status, age or smoking were excluded. A random forest model was used to identify features associated with PFS. Kaplan-Meier methods, Cox regression and logistic regression with receiver operating characteristics (ROC) and 5-fold cross-validated areas-under-the-curve (CV-AUCs) were used. A total of 114 patients were included. With median follow-up 40months (range: 3-138months), 14 patients had local recurrence, 21 had DM and 38 died. Two-year actuarial local control, distant control, PFS and overall survival was 89%, 84%, 70% and 84%, respectively. The wavelet_LHL_GLDZM_LILDE feature slightly improved PFS prediction compared to clinical features alone (CV-AUC 0.73 vs. 0.71). Age>65years (HR=2.64 (95%CI: 1.36-5.2), p=0.004) and p16-negative disease (HR=3.38 (95%CI: 1.72-6.66), p<0.001) were associated with poor PFS. A binary radiomic classifier strongly predicted DM with multivariable HR=3.27 (95%CI: 1.15-9.31), p=0.027, specifically for patients with p16-negative disease with 2-year DM-free survival 83% for low-risk vs. 38% for high-risk patients (p=0.004). A radiomics signature strongly associated with DM risk could provide a tool for improved risk stratification, potentially adding adjuvant immunotherapy for high-risk patients.

Texture analysis of PET images for predicting response to induction chemotherapy for oral squamous cell carcinoma

We evaluated whether texture analysis of positron emission tomography (PET) scans could predict the response to induction chemotherapy (ICT) in patients with oral squamous cell carcinoma (OSCC). Our retrospective cohort study included 21 patients with OSCC who underwent ICT. We extracted 31 textural indices from pretreatment PET scans and performed receiver operating characteristic curve (ROC) analysis to evaluate these indices’ efficacy in predicting ICT response. The area under the ROC curve was statistically significant for one texture index: short-zone emphasis (SZE; p = 0.041).

Positron Emission Tomography to Evaluate Response in the Cervix and Lymph Nodes after Definitive Chemoradiation and Immunotherapy for Cervical Cancer Patients Treated on GOG 9929

Positron emission tomography (PET) has been shown to be prognostic for response and survival after standard chemoradiation (CRT) for cervical cancer. We investigated the role of PET in evaluating the primary tumor and metastatic lymph nodes after CRT and immunotherapy for locally advanced cervical cancer (LACC) patients (pts) treated with standard chemoradiation (CRT) followed by ipilimumab on GOG 9929. Node positive LACC pts were prospectively enrolled and treated with 6 weekly doses of cisplatin (40 mg/m2) and extended field radiation therapy. A pretreatment PET scan was required. Two to 6 weeks after CRT completion, pts with no evidence of disease progression initiated ipilimumab once every 3 weeks for 4 planned doses. Two dose levels were evaluated: 3mg/kg (DL1) and 10mg/kg (DL2), with an expansion at 10mg/kg. Pts had a post ipilimumab PET scan at 4-12 weeks. Further investigation of the cervix pre and post therapy PET scan used two metrics: (a) standardized uptake value (SUV), and (b) ratio of post-therapy SUVmax: pre-therapy SUVmax. We then correlated the PET response with 1-year disease free and overall survival data. All radiation plans underwent RT quality review with a radiation oncologist specializing in gynecology oncology. Thirty-two of 34 enrolled pts initiated study treatment, of whom 18 pts have complete pre and post therapy PET data, with at least 1 dose of ipilimumab. Of the 18 pts, 89% were squamous histology; all had positive pelvic lymph nodes (PVLN), and 47% had positive para-aortic lymph nodes (PALN). All pts completed CRT, with ipilimumab completion rates of 72% with 4 cycles, 11% with 3 cycles, 11% with 2 cycles and 6% with 1 cycle. There were no minor or major RT quality deviations. 18 patients have a measure of post ipilimumab PET scan response for the cervix: 13 had a complete response (CR), three had a partial response (PR), and two had stable disease (SD). 17 patients have a measure of PET scan response for PVLN: 8 had a CR, 7 had a PR, and 2 had SD. 3 patients have a measure of PET scan response for PALN, and all had a CR. In the 18 patients, the 12-month OS is 94% and the 12-month RFS is 88%. In the 18 patients, there were 2 recurrences, one of whom died: one had a CR in both cervix and PVLN, with no PALN data; the pt who recurred and died had a CR in cervix and a PR in PVLN, with no PALN data. This study is the first to describe the use of PET imaging as a prognostic imaging biomarker for cervical cancer after CRT and immunotherapy. Our data suggests that the post therapy PET could be used as an early correlate of response, and a potential biomarker tool for clinical trials and practice in cervical cancer.

Prognostic value of baseline SUVmax in patients with advanced stage follicular lymphoma receiving frontline rituximab-based therapy.

7540 Background: Positron emission tomography (PET) is recommended in follicular lymphoma (FL) for initial staging, evaluation of potential transformation, and response assessment. The prognostic value of pre-treatment PET scan has not been adequately explored. Methods: We performed a single-institution retrospective analysis of patients with advanced stage FL, without histological evidence of transformation, treated with frontline rituximab-based therapy, and analyzed the prognostic significance of baseline maximum standardized uptake value (SUVmax). Results: The median follow-up for the cohort was 94 months. Of 346 patients, 151 (44%) received R-CHOP and 195 (56%) received non-R-CHOP regimens. Among multiple single unit increments of SUVmax, a value of &gt;18 showed the strongest association with progression-free survival (PFS) (hazard ratio [HR] 1.5, 95% confidence interval (CI) 0.95-2.3, p=0.08), and was selected as cut-off for further analysis. Fifty-two (15%) patients had a SUVmax &gt; 18. On univariate analysis, factors associated with SUVmax &gt; 18 were male sex (67% vs 52%, p=0.05), elevated β2-microglobulin (65% vs 47%, p=0.02), elevated LDH (37% vs 13%, p&lt;0.001), presence of B symptoms (35% vs 14%, p=0.01), and largest lymph node ≥ 6 cm (64% vs 30%, p&lt;0.001). On multivariate analysis, largest lymph node ≥ 6 cm was the only factor maintaining its association with SUVmax &gt; 18 (odds ratio [OR] 2.7, 95% CI 1.3-5.3, p=0.006). SUVmax &gt; 18 significantly associated with a lower CR rate among patients treated with non-R-CHOP regimens (45% vs 92%) (p&lt;0.001) but not among patients treated with R-CHOP (p=1). SUVmax &gt; 18 associated with significantly shorter PFS among patients treated with non-R-CHOP regimens (77 months vs not reached, p=0.02), but not among patients treated with R-CHOP (p=0.73). SUVmax &gt; 18 associated with shorter overall survival (OS) both in patients treated with R-CHOP (15 year OS 70% vs 75%, p=0.02) and non-R-CHOP regimens (15 year OS 50% vs 75%, p=0.001). Conclusions: In conclusion, baseline SUVmax has prognostic value in patients with advanced stage FL receiving rituximab-based therapies. Evaluation in prospective studies is needed to further confirm these findings.

Intratreatment Response Assessment With 18F-FDG PET: Correlation of Semiquantitative PET Features With Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiotherapy

This prospective study seeks to extract semiquantitative positron emission tomography (PET) features from 18F-fluorodeoxyglucose PET scans performed before and during neoadjuvant chemoradiotherapy for esophageal cancer and to compare their accuracy in predicting histopathologic response. From 2012 to 2016, 26 patients with esophageal cancer underwent pretreatment and intratreatment PET scans during chemoradiotherapy followed by surgery. Median patient age was 63years (interquartile range, 58-68years); 26 patients had esophageal adenocarcinoma, and 3 had esophageal squamous cell carcinoma. The intratreatment PET scan was performed at a median of 32.4Gy (interquartile range, 30.6-32.4Gy). PET features of the primary site including maximum standardized uptake value (SUV), SUV mean, metabolic tumor volume, and total lesion glycolysis were extracted from the pretreatment and intratreatment PET scans. Patients were histopathologic responders if there was complete or near-complete tumor response by modified Ryan scheme. Mean values of PET features were compared between histopathologic responders and nonresponders. The area under the receiver operating characteristic curve (AUC) was used to compare the accuracy of PET features in predicting histopathologic response. Eleven patients (42%) were histopathologic responders. PET features most discriminatory of histopathologic response on AUC analysis were volumetric PET features from the intratreatment PET including metabolic tumor volume based on manual contour (AUC, 0.73; 95% confidence interval, 0.52-0.93) and total lesion glycolysis based on semiautomatic 40% SUV threshold (AUC, 0.73; 95% confidence interval, 0.53-0.94). Volumetric PET features from the intratreatment PET were the most accurate predictors of histopathologic response.

18F-Fluorodeoxyglucose/Positron Emission Tomography Predicts Patterns of Failure After Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Wepreviously reported that pretreatment positron emission tomography (PET) identifies lesions at high risk for progression after concurrent chemoradiation therapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). Here we validate those findings and generate tumor control probability (TCP) models. We identified patients treated with definitive, concurrent CRT for locally advanced NSCLC who underwent staging 18F-fluorodeoxyglucose/PET/computed tomography. Visible hypermetabolic lesions (primary tumors and lymph nodes) were delineated on each patient's pretreatment PET scan. Posttreatment imaging was reviewed to identify locations of disease progression. Competing risks analyses were performed to examine metabolic tumor volume (MTV) and radiation therapy dose as predictors of local disease progression. TCP modeling was performed to describe the likelihood of local disease control as a function of lesion size. Eighty-nine patients with 259 hypermetabolic lesions (83 primary tumors and 176 regional lymph nodes) met the inclusion criteria. Twenty-eight patients were included in our previous report, and the remaining 61 constituted our validation cohort. The median follow-up time was 22.7months for living patients. In 20 patients, the first site of progression was a primary tumor or lymph node treated with radiation therapy. The median time to progression for those patients was 11.5months. Data from our validation cohort confirmed that lesion MTV predicts local progression, with a 30-month cumulative incidence rate of 23% for lesions above 25cc compared with 4% for lesions below 25cc (P=.008). We found no evidence that radiation therapy dose was associated with local progression risk. TCP modeling yielded predicted 30-month local control rates of 98% for a 1-cc lesion, 94% for a 10-cc lesion, and 74% for a 50-cc lesion. Pretreatment FDG-PET identifies lesions at risk for progression after CRT for locally advanced NSCLC. Strategies to improve local control should be tested on high-risk lesions, and treatment deintensification for low-risk lesions should be explored.

SU-F-R-27: Use Local Shape Descriptor Based On Geodesic Distance to Predict Survival in Non-Small Cell Lung Cancer After Radiotherapy

Purpose: The shape of the Positron Emission Tomography (PET) image represents the heterogeneity of tumor growth in various directions, and thus could be associated with tumor malignancy. We have proposed a median geodesic distance (MGD) to represent the local complexity of the shape and use a normalized MGD (NMGD) to quantify the shape, and found a potential correlation of NMGD to survival in a 20-patient pilot study. This study was to verify the finding in a larger patient cohort. Methods: Geodesic distance of two vertices on a surface is defined as the shortest path on the surface connecting the two vertices. The MGD was calculated for each vertex on the surface to display the local complexity of the shape. The NMGD was determined as: NMGD = 100*standard deviation(MGDs)/mean(MGDs). We applied the NMGD to 40 NSCLC patients who were enrolled in prospective PET image protocols and received radiotherapy. Each patient had a pre-treatment PET scan with the resolution of 4mm*4mm*5mm. Tumors were contoured by a professional radiation oncologist and triangulation meshes were built up based on the contours. Results: The mean and standard deviation of NMGD was 6.4±3.0. The OS was 33.1±16.9 months for low NMGD group, and 15.4±15.6 months for the high NMGD group. The low NMGD group had significant better OS than the high NMGD group (p=0.0013). Conclusion: NMGD could be used as a shape biomarker to predict survival and the MGD could be combined with image texture in future to increase prediction accuracy. This study was supported by Award Number 1R01CA166948 from the NIH and National Cancer Institute.

Prognostic Value of Preradiotherapy 18F-FDG PET/CT Volumetrics in Limited-Stage Small-Cell Lung Cancer

BackgroundWhether 18F-fludeoxyglucose positron emission tomography (PET)/computed tomography (CT) metrics predict outcome in limited-stage (LS) small-cell lung cancer (SCLC) has not been well established; most previous reports have only analyzed maximal standardized uptake values (SUVmax). We investigated multiple pretreatment PET metrics, including SUVmax, mean SUV (SUVmean), total lesion glycolysis, and metabolic tumor volume (MTV) in LS-SCLC patients undergoing chemoradiotherapy (CRT) and correlated them with survival and disease control outcomes. Patients and MethodsAll patients received platinum-based chemotherapy and a median radiation dose of 45 Gy. Kaplan-Meier and competing-risks analyses were performed to assess the prognostic value of PET metrics with respect to overall survival (OS), distant failure (DF), disease-free survival (DFS), and locoregional failure (LRF). Univariate and multivariate analyses were performed to account for the effect of other clinical factors on outcomes. ResultsA total of 120 patients with LS-SCLC had analyzable pre-CRT PET/CTs. The median follow up was 34 months. Median OS was 26.9 months. OS was 53.2% at 2 years and 33.1% at 5 years. SUVmax, SUVmean, MTV, and total lesion glycolysis of the primary tumor were not significantly associated with OS, LRF, and DFS on univariate analysis. MTV was significantly associated with DF (P = .024) on univariate but not multivariate analysis. ConclusionThis is the largest reported series to date evaluating the prognostic value of baseline PET metrics in LS-SCLC. Neither SUVmax nor other analyzed PET metrics demonstrated significant correlation with OS or LRF. MTV was correlated with DF and DFS, but this association was no longer significant after adjustment for other clinical factors. This analysis suggests that pretreatment PET scans, even with the use of advanced metrics, do not have independent prognostic value for outcomes in LS-SCLC patients after CRT.

Evaluation of factors associated with loco-regional failure and survival in limited disease small cell lung cancer patients treated with chemoradiotherapy

ABSTRACTBackground. Loco-regional failure (LRF) remains a significant problem in limited disease small cell lung cancer (LD-SCLC) patients treated with definitive chemoradiotherapy. Dose-escalation may be a way forward to reduce the failure rate. However, the risk of toxicity rises with increasing doses. Knowledge on factors associated with LRF could aid the selection of patients for more aggressive treatment. Therefore, the aim of this study is to evaluate factors correlated with LRF in a cohort of LD-SCLC patients treated with definitive chemoradiotherapy. Moreover, factors associated with improved survival were investigated.Material and methods. We included 147 consecutive LD-SCLC patients treated from 2007 to 2013. Radiotherapy was delivered as either 45 Gy in 1.5-Gy fractions twice daily or 46–50 Gy in 2-Gy fractions once daily. Chemotherapy was etoposide combined with either carboplatin or cisplatin given mainly concomitantly with radiotherapy. Pattern of first failure and survival were evaluated retrospectively. Cumulative LRF (CLRF) and overall survival (OS) were calculated by the Kaplan-Meier method. The impact of covariates on LRF and OS was evaluated by using Cox proportional hazards model.Results. With a median follow-up time of 42.2 months, 37 patients experienced LRF as first failure. Isolated LRF was seen in 16 patients, but no isolated regional failure was seen. The CLRF rate was 22% at 1-year and 43% at 3-years. N3-stage was an independent prognostic factor correlated with LRF development (p = 0.043). Median OS was 24.1 months (95% CI 19–29 months) and a three-year survival of 34%. Prognostic factors associated with improved OS were staging including a positron emission tomography (PET) scan (p = 0.004) and receiving prophylactic cranial irradiation (PCI) (p = 0.006).Conclusion. N3-stage was an independent prognostic factor for LRF. Receiving a pretreatment PET scan and receiving PCI were prognostic factors for improved OS. Reduction in LRF may be achieved with dose-escalation in patients with N3-stage. This can be evaluated in prospective dose-escalation trials.

PET Could Predict Response to Neoadjuvant Therapy and Long‐Term Survival of Patients with Esophageal Cancer

Dear Editor, We have read with the great interest the article by Brown et al. [1] entitled ‘‘Accuracy of PET-CT in predicting survival in patients with esophageal cancer’’: They concluded that ‘‘This study does not support the use of SUVmax on pretreatment PET scans as a prognostic tool for patients with esophageal cancer, especially in those who have received neoadjuvant therapy.’’ However, we have several concerns about their conclusion. Many articles have already reported on the use of positron emission tomography (PET) in pretreatment evaluation of esophageal cancer, as was mentioned in the Brown et al. report [1]. Metabolic activity of carcinoma could be evaluated by measuring tumor glucose metabolism with the glucose analog [18F]fluorodeoxyglucose (FDG) [2]. There is accumulating evidence that supports the fact that the pathologic response after neoadjuvant therapy is the major determinant of long-term survival of patients with esophageal cancer. Patients treated with neoadjuvant therapy who achieve pathologic complete response (pCR) have a significantly higher rate of complete resection, fewer recurrences, and improved 5-year overall survival and disease-free survival [3]. However, in the Brown et al. report there was a lack of analysis on the pCR subgroup and no discussion about the relationship between the pretreatment standard uptake value (SUV) and the pathologic response. Furthermore, PET could predict the pathologic response by comparing the SUVs from before and after neoadjuvant therapy, not just the pretreatment SUV. Ott et al. [2] classified patients as metabolic responders when tumor metabolic activity had decreased by more than 35 % 2 weeks after the end of neoadjuvant therapy. Metabolic responders showed a high pathologic response rate (44 %), with a 3-year survival rate of 70 %, compared to metabolic nonresponders with a pathologic response rate of 5 % (P = 0.001) and a 3-year survival rate of 35 % (P = 0.01). Brucher et al. [4] analyzed pathologic responses after neoadjuvant therapy. In pathologic responders, the SUV decreased by 72 ± 11 %, while in pathologic nonresponders it decreased by only 42 ± 22 % (P \ 0.05), between pretreatment and 3 weeks after the end of neoadjuvant therapy. Nonresponders to PET scanning had a significantly worse survival rate after resection than responders. The data from Flamen et al. [5] further found that the agreement between the assessment of the change in tumor activity by PET preand post-neoadjuvant therapy and pathologic evaluation could achieve 78 %. Therefore, we believe that PET scanning could predict the response to neoadjuvant therapy and the long-term survival of the patients with esophageal cancer. It is feasible to predict the pathologic response of neoadjuvant therapy by assessing the SUV reduction ratio before and after treatment and thereby predict long-term survival. The SUV reduction ratio and the pathologic response, which have been ignored by authors, are two crucial factors

Accuracy of PET‐CT in Predicting Survival in Patients with Esophageal Cancer

Positron emission tomography (PET) is an integral part of tumor staging for patients with esophageal cancer. Recent studies suggest a role for PET scan in predicting survival in these patients, but this relationship is unclear in the setting of neoadjuvant therapy. We examined pretreatment maximum standard uptake value (SUV(max)) of the primary tumor in patients treated with and without neoadjuvant therapy. All patients undergoing esophagectomy with a preoperative PET scan over a nine-year period (2001-2010) were identified from a prospectively maintained database. Positron emission tomography data were obtained from computers housing the original PET scans. Overall survival was correlated with SUV(max) of the primary tumor. A total of 191 patients were identified, and 103 patients met inclusion criteria. Eighty-two had an adenocarcinoma (80%), and 21 (20%) had a squamous cell carcinoma. Fifty-seven (55%) patients received neoadjuvant therapy. In the surgery alone group, a SUV(max) of > 5.0 in the primary tumor was associated with poor prognosis [Hazard Ratio (HR) 0.32; p = 0.007], but this factor did not retain its significance on multivariate analysis (HR 0.65; p = 0.43). Pretreatment SUV(max) in patients who underwent neoadjuvant therapy was not significant in predicting overall survival (p = 0.10). This study does not support the use of SUV(max) on pretreatment PET scans as a prognostic tool for patients with esophageal cancer, especially in those who have received neoadjuvant therapy. Lymph node status is a more accurate predictor of outcome, and efforts to improve pretreatment staging should focus on this factor.

Utility of positron emission tomography scans in mantle cell lymphoma

Positron emission tomography (PET) scans are widely used in patients with lymphoma but little is known about their utility in mantle cell lymphoma (MCL). MCL patients were included from two prospective trials and one observational study at our institution. A total of 276 PET scans were performed among 52 patients. After a median follow-up of 37.5 months, the 3-year event-free survival (EFS) and overall survival (OS) were 73% (95% confidence interval [CI]: 61-85%) and 92% (95% CI 85-100%), respectively. There were 34 pretreatment PET scans, 26 interim, 28 end-of-treatment, 162 surveillance, and 26 scans at relapse or beyond. Pretreatment PETs were positive in 94%. A negative interim or end-of-therapy PET scan was not significantly associated with better EFS or OS, but no deaths were observed in patients who had a negative interim or end-of-therapy PET. Surveillance PET scans had a high false positive rate (35%) and low positive predictive value (8%). PET scans contributed to an earlier diagnosis of relapse in only two out of the 18 patients (11%) who relapsed. PET scans did not meaningfully contribute to staging or surveillance of MCL patients in this study. There was a trend toward improved survival in patients who had a negative end-of-therapy PET scan.

Pretreatment positron emission tomography (PET) scan standardized uptake value (SUV) as a prognostic variable for overall survival in limited-stage small cell lung cancer (L-SCLC).

7045 Background: PET imaging has been increasingly utilized in L-SCLC. However, the prognostic value of the staging SUV has not been well elucidated. Methods: From 1/2004-12/2008, 59 patients with L-SCLC were treated with definitive chemoradiation at M. D. Anderson Cancer Center and received a pretreatment staging PET scan. The median radiation therapy (RT) dose was 45 Gy in 30 fractions delivered twice daily (range 40.5-61.8 Gy). Thirty two percent of patients (n = 19) underwent induction chemotherapy, though all initial PET scans were taken prior to any treatment. The median value for the maximum SUV of the primary lesion (pSUVmax) was 12.0 (range 1.3-34.6), and for the nodal disease (nSUVmax) it was 11.5 (range 3.1-35.5). Twenty eight percent of patients had assessable follow-up PET imaging within one year of completing treatment. Overall survival (OS) was measured from the end of RT to the date of death or, if not documented, the last follow-up at our institution. Kaplan-Meier analysis was utilized to determine 1, 2, and 3-year estimates of OS. Univariate analysis was then performed to evaluate the effect of pSUVmax and nSUVmax on OS. Results: The median change in pSUVmax after treatment was -63% (range +21 to -90%). At a median follow-up of 16.4 months (range 2.9-68.5 months), 1-, 2-, and 3-year rates of OS were 74%, 60%, and 46%, respectively. On univariate analysis, a pSUVmax of > 13 was of borderline significance (p = 0.05), and a pSUVmax of >14 was statistically significant as a prognostic factor for OS (p < 0.05). A higher pSUVmax was correlated with an improved survival up to a level of 18. At pSUVmax>18, small patient numbers limited analysis. Initial nSUVmax did not correlate with OS. Conclusions: Most patients who receive definitive chemotherapy and RT for L-SCLC experience marked PET scan responses. Unexpectedly, a higher initial pSUVmax was associated with better OS. This finding could be due to improved outcomes with accelerated RT in high-SUV patients, such that there is a more beneficial fractionation for patients with low SUVmax levels in L-SCLC. Individualized treatment may be indicated based on pretreatment SUV. No significant financial relationships to disclose.

Primary gastric diffuse large B‐cell Lymphoma (DLBCL): analyses of prognostic factors and value of pretreatment FDG‐PET scan

We report a single institution experience with gastric diffuse large B-cell lymphoma (DLBCL) in an attempt to evaluate the roles of different treatment modalities, to assess the value of pretreatment positron emission tomography (PET) scan, and to identify potential prognostic factors. Among 384 patients diagnosed with DLBCL between 1995 and 2008, 75 patients had primary gastric DLBCL and were reviewed and analyzed. The median age was 66. International prognostic index (IPI) risk was low in 52%, low-intermediate in 23%, high-intermediate in 9%, and high in 16%. Pretreatment PET scan was highly sensitive in detecting gastric lesions except stage I gastric DLBCL without detectable mass by CT or gastroscopy. As a general rule, patients with limited-stage disease were treated with three times of CHOP (with or without rituximab) and radiotherapy, and those with advanced-stage disease were treated with eight cycles of CHOP (with or without rituximab), and radiotherapy was given to residual diseases after chemotherapy. Three-year overall survival (OS) rate was 78%. Multivariate analysis revealed that low albumin, hemoglobin <12.0 g/dL, and treatment without rituximab were independently associated with shorter OS. Low albumin, hemoglobin <12.0 g/dL,and advanced stage were independently associated with shorter progression-free survival. We showed the survival benefit of rituximab and potential prognostic value of pretreatment hemoglobin and serum albumin levels in gastric DLBCL.

Selective Nodal Irradiation on Basis of 18FDG-PET Scans in Limited-Disease Small-Cell Lung Cancer: A Prospective Study

To evaluate the results of selective nodal irradiation on basis of (18)F-deoxyglucose positron emission tomography (PET) scans in patients with limited-disease small-cell lung cancer (LD-SCLC) on isolated nodal failure. A prospective study was performed of 60 patients with LD-SCLC. Radiotherapy was given to a dose of 45 Gy in twice-daily fractions of 1.5 Gy, concurrent with carboplatin and etoposide chemotherapy. Only the primary tumor and the mediastinal lymph nodes involved on the pretreatment PET scan were irradiated. A chest computed tomography (CT) scan was performed 3 months after radiotherapy completion and every 6 months thereafter. A difference was seen in the involved nodal stations between the pretreatment (18)F-deoxyglucose PET scans and computed tomography scans in 30% of patients (95% confidence interval, 20-43%). Of the 60 patients, 39 (65%; 95% confidence interval [CI], 52-76%) developed a recurrence; 2 patients (3%, 95% CI, 1-11%) experienced isolated regional failure. The median actuarial overall survival was 19 months (95% CI, 17-21). The median actuarial progression-free survival was 14 months (95% CI, 12-16). 12% (95% CI, 6-22%) of patients experienced acute Grade 3 (Common Terminology Criteria for Adverse Events, version 3.0) esophagitis. PET-based selective nodal irradiation for LD-SCLC resulted in a low rate of isolated nodal failures (3%), with a low percentage of acute esophagitis. These findings are in contrast to those from our prospective study of CT-based selective nodal irradiation, which resulted in an unexpectedly high percentage of isolated nodal failures (11%). Because of the low rate of isolated nodal failures and toxicity, we believe that our data support the use of PET-based SNI for LD-SCLC.

Metabolic Tumor Volume Predicts for Recurrence and Death in Head-and-Neck Cancer

To evaluate the prognostic value of metabolic tumor volume measured on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and other clinical factors in patients treated for locally advanced head-and-neck cancer (HNC) at a single institution. Between March 2003 and August 2007, 85 patients received positron emission tomography (PET)/computed tomography-guided chemoradiotherapy for HNC. Metabolically active tumor regions were delineated on pretreatment PET scans semiautomatically using custom software. We evaluated the relationship of (18)F-fluorodeoxyglucose-PET maximum standardized uptake value (SUV) and total metabolic tumor volume (MTV) with disease-free survival (DFS) and overall survival (OS). Mean follow-up for surviving patients was 20.4 months. The estimated 2-year locoregional control, DFS, and OS for the group were 88.0%, 69.5%, and 78.4%, respectively. The median time to first failure was 9.8 months among the 16 patients with relapse. An increase in MTV of 17.4 mL (difference between the 75th and 25th percentiles) was significantly associated with an increased hazard of first event (recurrence or death) (1.9-fold, p < 0.001), even after controlling for Karnofsky performance status (KPS) (1.8-fold, p = 0.001), and of death (2.1-fold, p < 0.001). We did not find a significant relationship of maximum SUV, stage, or other clinical factors with DFS or OS. Metabolic tumor volume is an adverse prognostic factor for disease recurrence and death in HNC. MTV retained significance after controlling for KPS, the only other significant adverse prognostic factor found in this cohort. MTV is a direct measure of tumor burden and is a potentially valuable tool for risk stratification and guiding treatment in future studies.

Reproducibility of Intratumor Distribution of 18F-Fluoromisonidazole in Head and Neck Cancer

Hypoxia is one of the main causes of the failure to achieve local control using radiotherapy. This is due to the increased radioresistance of hypoxic cells. (18)F-fluoromisonidazole ((18)F-FMISO) positron emission tomography (PET) is a noninvasive imaging technique that can assist in the identification of intratumor regions of hypoxia. The aim of this study was to evaluate the reproducibility of (18)F-FMISO intratumor distribution using two pretreatment PET scans. We enrolled 20 head and neck cancer patients in this study. Of these, 6 were excluded from the analysis for technical reasons. All patients underwent an (18)F-fluorodeoxyglucose study, followed by two (18)F-FMISO studies 3 days apart. The hypoxic volumes were delineated according to a tumor/blood ratio >or=1.2. The (18)F-FMISO tracer distributions from the two (18)F-FMISO studies were co-registered on a voxel-by-voxel basis using the computed tomography images from the PET/computed tomography examinations. A correlation between the (18)F-FMISO intensities of the corresponding spatial voxels was derived. A voxel-by-voxel analysis of the (18)F-FMISO distributions in the entire tumor volume showed a strong correlation in 71% of the patients. Restraining the correlation to putatively hypoxic zones reduced the number of patients exhibiting a strong correlation to 46%. Variability in spatial uptake can occur between repeat (18)F-FMISO PET scans in patients with head and neck cancer. Blood data for one patient was not available. Of 13 patients, 6 had well-correlated intratumor distributions of (18)F-FMISO-suggestive of chronic hypoxia. More work is required to identify the underlying causes of changes in intratumor distribution before single-time-point (18)F-FMISO PET images can be used as the basis of hypoxia-targeting intensity-modulated radiotherapy.